title: Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.
abstract: BACKGROUND
  Various cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA.
  
  
  METHODS
  Polymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed.
  
  
  RESULTS
  The IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity.
  
  
  CONCLUSIONS
  We here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. m.emonts@erasmusmc.nl
authors.forename: Marieke
authors.initials: M
authors.lastname: Emonts
authors.forename: Mieke J M W
authors.initials: MJ
authors.lastname: Hazes
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
authors.forename: Christa E
authors.initials: CE
authors.lastname: van der Gaast-de Jongh
authors.forename: Lisette
authors.initials: L
authors.lastname: de Vogel
authors.forename: Huub K H
authors.initials: HK
authors.lastname: Han
authors.forename: Jacques M G W
authors.initials: JM
authors.lastname: Wouters
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Radboud J E M
authors.initials: RJ
authors.lastname: Dolhain
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D018836:Inflammation Mediators; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018836:Inflammation Mediators; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha